Dr. Sascha Dublin is a Senior Fellow in General Internal Medicine at the University of Washington. She seeks to develop a career studying medication risks and benefits in the elderly. The elderly are often excluded from clinical trials, and thus observational studies-which may have important biases- are often the only source for information about medication effects in this population. Dr. Dublin will address a key methodologic problem in this field: bias due to confounding by cognitive and functional status. Through this award, she proposes to 1) gain additional background in aging research through didactic instruction;2) pursue advanced training in relevant aspects of clinical geriatrics;and 3) conduct mentored research guided by her sponsors Drs. Eric Larson and Noel Weiss, distinguished researchers in the field of aging. RESEARCH: The goal of Dr. Dublin's research is two-fold. First, she will investigate associations between use of specific medications-acid-suppressing medications, benzodiazepines, angiotensin-converting enzyme inhibitors (ACEIs), and statins-and risk of pneumonia, a common and serious illness. Second, she will use this research to examine the impact of functional and cognitive status as confounders in studies of medication effects in the elderly. The results of some prior studies suggest that acid-suppressing medications and benzodiazepines are associated with increased pneumonia risk, while ACEIs and statins are associated with decreased risk. However, residual bias related to cognitive and functional impairment could explain all of these associations. She will carry out 3 linked projects within the Adult Changes in Thought cohort study, which includes more than 3300 elderly persons with 22,000 person-years of follow-up. Project 1 examines use of these 4 medication classes in relation to cognitive and functional impairment, and Project 2 evaluates cognitive and functional impairment as risk factors for pneumonia. Finally, Project 3 examines pneumonia risk in relation to use of these 4 medication classes, with adjustment for confounders including cognitive and functional status and comorbid illness. SIGNIFICANCE: This work will provide pilot data for future proposals and establish a direction for Dr. Dublin's future research career. It also will provide information on potentially reversible causes of pneumonia, a common and often devastating illness, and contribute to improved methods in studies of medication effects in the elderly.